US6649796B2 - Process for the preparation of acetamide derivatives - Google Patents
Process for the preparation of acetamide derivatives Download PDFInfo
- Publication number
- US6649796B2 US6649796B2 US10/112,776 US11277602A US6649796B2 US 6649796 B2 US6649796 B2 US 6649796B2 US 11277602 A US11277602 A US 11277602A US 6649796 B2 US6649796 B2 US 6649796B2
- Authority
- US
- United States
- Prior art keywords
- diphenylmethylthioacetamide
- preparation
- formula
- water
- reacting
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 150000003869 acetamides Chemical class 0.000 title 1
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical class NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims abstract description 21
- HCRQRIFRHGPWBH-UHFFFAOYSA-N 2-benzhydrylsulfanylacetamide Chemical compound C=1C=CC=CC=1C(SCC(=O)N)C1=CC=CC=C1 HCRQRIFRHGPWBH-UHFFFAOYSA-N 0.000 claims abstract description 14
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000002585 base Substances 0.000 claims abstract description 7
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 4
- 150000001340 alkali metals Chemical class 0.000 claims abstract description 4
- 150000001450 anions Chemical class 0.000 claims abstract description 4
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 125000005843 halogen group Chemical group 0.000 claims abstract description 4
- YFGHCGITMMYXAQ-UHFFFAOYSA-N 2-[(diphenylmethyl)sulfinyl]acetamide Chemical compound C=1C=CC=CC=1C(S(=O)CC(=O)N)C1=CC=CC=C1 YFGHCGITMMYXAQ-UHFFFAOYSA-N 0.000 claims description 11
- 229960001165 modafinil Drugs 0.000 claims description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 125000004436 sodium atom Chemical group 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- QILSFLSDHQAZET-UHFFFAOYSA-N diphenylmethanol Chemical compound C=1C=CC=CC=1C(O)C1=CC=CC=C1 QILSFLSDHQAZET-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 239000000725 suspension Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 230000037361 pathway Effects 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000010268 HPLC based assay Methods 0.000 description 5
- VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 0 *.*CC(N)=O.C.CO.I.N=C(N)SC(C1=CC=CC=C1)C1=CC=CC=C1.NC(=O)CSC(C1=CC=CC=C1)C1=CC=CC=C1.[V]I Chemical compound *.*CC(N)=O.C.CO.I.N=C(N)SC(C1=CC=CC=C1)C1=CC=CC=C1.NC(=O)CSC(C1=CC=CC=C1)C1=CC=CC=C1.[V]I 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- LRBMHUPFZBPGTG-UHFFFAOYSA-N [amino(sulfanyl)methylidene]-benzhydrylazanium;bromide Chemical compound [Br-].C=1C=CC=CC=1C([NH+]=C(S)N)C1=CC=CC=C1 LRBMHUPFZBPGTG-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- BIASHYVHAQBNGV-UHFFFAOYSA-N 3,3-diphenylpropanethioic s-acid Chemical compound C=1C=CC=CC=1C(CC(=S)O)C1=CC=CC=C1 BIASHYVHAQBNGV-UHFFFAOYSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical compound NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 description 1
- ZNTZDLKAWLXDKF-UHFFFAOYSA-N 3,3-diphenylpropanethioyl chloride Chemical compound C=1C=CC=CC=1C(CC(=S)Cl)C1=CC=CC=C1 ZNTZDLKAWLXDKF-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- DANHJTSBKHDHDZ-UHFFFAOYSA-M Br.Br.C.II.N=C(N)SC(C1=CC=CC=C1)C1=CC=CC=C1.NC(N)=S.O=C(O)CCl.OC(C1=CC=CC=C1)C1=CC=CC=C1.[V]I Chemical compound Br.Br.C.II.N=C(N)SC(C1=CC=CC=C1)C1=CC=CC=C1.NC(N)=S.O=C(O)CCl.OC(C1=CC=CC=C1)C1=CC=CC=C1.[V]I DANHJTSBKHDHDZ-UHFFFAOYSA-M 0.000 description 1
- ZFSZFYGQEABYIY-UHFFFAOYSA-N COC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1.CS(C)(=O)(O)OO.II.I[IH]I.N.NC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1.O.O.O=C(O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1 Chemical compound COC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1.CS(C)(=O)(O)OO.II.I[IH]I.N.NC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1.O.O.O=C(O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1 ZFSZFYGQEABYIY-UHFFFAOYSA-N 0.000 description 1
- KNLVMAIIQHIVOA-UHFFFAOYSA-N I.II.I[IH]I.N.NC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1.NC(=O)CSC(C1=CC=CC=C1)C1=CC=CC=C1.O.O.O=C(Cl)CSC(C1=CC=CC=C1)C1=CC=CC=C1.O=S(Cl)Cl Chemical compound I.II.I[IH]I.N.NC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1.NC(=O)CSC(C1=CC=CC=C1)C1=CC=CC=C1.O.O.O=C(Cl)CSC(C1=CC=CC=C1)C1=CC=CC=C1.O=S(Cl)Cl KNLVMAIIQHIVOA-UHFFFAOYSA-N 0.000 description 1
- HTHFEDOFDBZPRX-UHFFFAOYSA-N O=C(O)CSC(C1=CC=CC=C1)C1=CC=CC=C1 Chemical compound O=C(O)CSC(C1=CC=CC=C1)C1=CC=CC=C1 HTHFEDOFDBZPRX-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 229940106681 chloroacetic acid Drugs 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 229940117394 provigil Drugs 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
Definitions
- the present invention relates to an improved process for the preparation of diphenylmethylthioacetamide (I), a key intermediate in the synthetic pathway for Modafinil.
- Modafinil is defined as a CNS stimulant and is marketed under the trade name “Provigil”, for the treatment of narcolepsia.
- Modafinil was introduced by Lafon. Its preparation, use and pharmacological properties were described in U.S. Pat. No. 4,177,290.
- Compound II is prepared by the reaction of diphenylmethanol with thiourea in the presence of HBr followed by basic hydrolysis and reaction with chloroacetic acid (Scheme 3).
- both pathways involve toxic and dangerous reagents such as dimethylsulfate, ammonia and thionyl chloride.
- haloacetamide reacts with the isothiouronium salt (IV) in protic solvents (like alcohols or water) at temperatures ranging from 0-100° C. in the presence of a strong base, such as alkali metal hydroxide.
- chloracetamide is reacted with the said isothiouronium salt in water at 60-70° C. using sodium hydroxide as base.
- diphenylmethylthioacetamide is obtained in 95% yield from diphenylmethanol.
- a process for the preparation of diphenylmethylthioacetamide (I) as described in Scheme 4 comprising reacting of the isothiouronium salt or its corresponding base of the formula IV with an acetamide of the formula XCH 2 CONH 2 , wherein X represents a halogen, M represents an alkali metal and A represents an anion, in a protic medium at a temperature of less than 100° C.
- the said method comprises only three chemical steps. It does not involve toxic or corrosive reagents. Very pure Modafinil is obtained at the end of the synthetic pathway at 67% yield (starting from diphenylmethanol).
- diphenylmethanol is reacted with thiourea in the presence of hydrobromic acid in aqueous medium under reflux and then cooled.
- the isothiouronium salt (IV) formed is filtered and reacted with chloroacetamide under aqueous base conditions at 60-70° C. The solution is cooled and the diphenylmethylthioacetamide formed is filtered and collected.
- Diphenylmethanol (130 g, 0.7 mole) and thiourea (65 g, 0.85 mole) are added in 0.5 l reactor charging with water (325 ml).
- the mixture is heated to 95° C. (an emulsion is obtained) and 48% HBr 260 gr. 3.22 mole, 4.6 equivalents) is then added gradually during 0.5 hour.
- the mixture is heated under reflux (106-107° C.) for 0.5 hour and cooled to 80-85° C. At this temperature, the mixture is seeded with several crystals of the product and the mixture is stirred at that temperature for 0.5 hour and then cooled to 250.
- the colorless crystals are collected by filtration, washed with water (200 ml) yielding about 240 gr. of wet crude isothiouronium salt.
- a 2 L reactor was charged with diphenylmethylisothiouronium bromide crude wet obtained in reference example 1 (240 gr.) and water (700 ml.) under nitrogen.
- the suspension was heated to 60° C. and 46% aqueous NaOH solution (98 ml, 1.68 mole, 2.4 eq.) was added.
- the reaction mixture was heated to 85° C. and stirred until all the solid was dissolved.
- the suspension is stirred at 70° C. for 4-5 hours.
- a 0.5 L reactor was charged with diphenylmethylisothiouronium bromide crude wet (61 g.) and methanol (163 ml.) under nitrogen. The suspension was heated to 40-50° C. and 46% aqueous NaOH solution (25 ml.) was added. The reaction mixture was heated to 60° C. and stirred for 1 ⁇ 2 hour. Chloroacetamide (19.8 g, 0.21 mole, 1.2 eq., purity 98%) was added in two portions during 10 minutes. The suspension was stirred at heating under reflux for 3-4 hours. Then water (80 ml.) was added dropwise at 60-65° C. The mixture was cooled to 30° C. and filtered.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL143,106 | 2001-05-13 | ||
| IL14310601A IL143106A (en) | 2001-05-13 | 2001-05-13 | Process for the preparation of diphenylmethylthioacetamide |
| IL143106 | 2001-05-13 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| US20020183552A1 US20020183552A1 (en) | 2002-12-05 |
| US6649796B2 true US6649796B2 (en) | 2003-11-18 |
Family
ID=11075391
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US10/112,776 Expired - Lifetime US6649796B2 (en) | 2001-05-13 | 2002-04-02 | Process for the preparation of acetamide derivatives |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US6649796B2 (xx) |
| EP (1) | EP1260501A1 (xx) |
| CA (1) | CA2378418C (xx) |
| IL (1) | IL143106A (xx) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040002547A1 (en) * | 2002-05-23 | 2004-01-01 | Denis Largeau | Preparations of a sulfinyl acetamide |
| US20040106829A1 (en) * | 2002-11-12 | 2004-06-03 | Procos S.P.A. | Process for the synthesis of modafinil |
| US20040253308A1 (en) * | 2003-04-29 | 2004-12-16 | Barr Laboratories, Inc. | Surface-treated modafinil particles |
| US20050034652A1 (en) * | 2000-07-27 | 2005-02-17 | Arina Ceausu | Crystalline forms of modafinil |
| US20060128812A1 (en) * | 2003-01-31 | 2006-06-15 | Alembic Limited | Process for the preparation of 2-[(diphenylmethyl) thio] acetamide |
| US20060160903A1 (en) * | 2003-02-24 | 2006-07-20 | Sidney Liang | Process for preparing benzhydrylthioacetamide |
| US20070293702A1 (en) * | 2006-02-21 | 2007-12-20 | Viviana Braude | Novel crystalline forms of armodafinil and preparation thereof |
| US20080031939A1 (en) * | 2006-03-01 | 2008-02-07 | Viviana Braude | Process for the preparation of armodafinil |
| US20090048464A1 (en) * | 2007-08-16 | 2009-02-19 | Boaz Gome | Purification of armodafinil |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1670753A4 (en) * | 2003-09-04 | 2008-01-02 | Cephalon Inc | MODAFINIL COMPOSITIONS |
| WO2005046854A2 (en) * | 2003-09-12 | 2005-05-26 | Sun Pharmaceutical Industries Limited | A process for the preparation of diphenylmethylsulfinyl derivatives |
| EP1516869A1 (en) | 2003-09-19 | 2005-03-23 | Cephalon France | Process for enantioselective synthesis of single enantiomers of modafinil by asymmetric oxidation |
| US7368591B2 (en) | 2003-09-19 | 2008-05-06 | Cephalon France | Process for enantioselective synthesis of single enantiomers of modafinil by asymmetric oxidation |
| CA2632722A1 (en) * | 2005-12-09 | 2007-06-21 | Mallinckrodt Inc. | Processes for the preparation of modafinil and analogs thereof |
| CN102976985A (zh) * | 2011-09-07 | 2013-03-20 | 大连大学 | 一锅法合成二苯甲基亚磺酰基乙酰胺及其类似物的方法 |
| ES2645483T3 (es) | 2014-08-13 | 2017-12-05 | Red Bull Gmbh | Compuestos heterocíclicos con actividad de mejora de la memoria de trabajo |
| CA2989243C (en) | 2014-08-13 | 2023-03-14 | Red Bull Gmbh | Heterocyclic compounds with working memory enhancing activity |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4177290A (en) | 1977-03-31 | 1979-12-04 | Laboratoire L. Lafon | Acetamide derivatives |
| FR2528038A2 (fr) * | 1982-06-04 | 1983-12-09 | Lafon Labor | Derives de benzhydrylsulfinylacetamide et leur utilisation en therapeutique |
-
2001
- 2001-05-13 IL IL14310601A patent/IL143106A/xx not_active IP Right Cessation
-
2002
- 2002-03-22 CA CA002378418A patent/CA2378418C/en not_active Expired - Fee Related
- 2002-04-02 US US10/112,776 patent/US6649796B2/en not_active Expired - Lifetime
- 2002-04-18 EP EP02008248A patent/EP1260501A1/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4177290A (en) | 1977-03-31 | 1979-12-04 | Laboratoire L. Lafon | Acetamide derivatives |
| FR2528038A2 (fr) * | 1982-06-04 | 1983-12-09 | Lafon Labor | Derives de benzhydrylsulfinylacetamide et leur utilisation en therapeutique |
Cited By (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7235691B2 (en) | 2000-07-27 | 2007-06-26 | Teva Pharmaceutical Industries Ltd. | Crystalline forms of modafinil |
| US8048222B2 (en) | 2000-07-27 | 2011-11-01 | Teva Pharmaceutical Industries, Ltd. | Highly pure modafinil |
| US20050034652A1 (en) * | 2000-07-27 | 2005-02-17 | Arina Ceausu | Crystalline forms of modafinil |
| US20050038124A1 (en) * | 2000-07-27 | 2005-02-17 | Arina Ceausu | Highly pure modafinil |
| US6875893B2 (en) * | 2002-05-23 | 2005-04-05 | Cephalon, Inc. | Preparations of a sulfinyl acetamide |
| US20050171209A1 (en) * | 2002-05-23 | 2005-08-04 | Cephalon, Inc. | Preparations of a sulfinyl acetamide |
| US7057069B2 (en) * | 2002-05-23 | 2006-06-06 | Cephalon, Inc. | Preparations of a sulfinyl acetamide |
| US20040002547A1 (en) * | 2002-05-23 | 2004-01-01 | Denis Largeau | Preparations of a sulfinyl acetamide |
| US20040106829A1 (en) * | 2002-11-12 | 2004-06-03 | Procos S.P.A. | Process for the synthesis of modafinil |
| US20060128812A1 (en) * | 2003-01-31 | 2006-06-15 | Alembic Limited | Process for the preparation of 2-[(diphenylmethyl) thio] acetamide |
| US7186860B2 (en) * | 2003-01-31 | 2007-03-06 | Alembic Limited | Process for the preparation of 2-[(diphenylmethyl) thio] acetamide |
| US20060160903A1 (en) * | 2003-02-24 | 2006-07-20 | Sidney Liang | Process for preparing benzhydrylthioacetamide |
| US7244865B2 (en) | 2003-02-24 | 2007-07-17 | Mallinckrodt Inc. | Process for preparing benzhydrylthioacetamide |
| US20100112045A1 (en) * | 2003-04-29 | 2010-05-06 | Cephalon, Inc. | Surface-treated modafinil particles |
| US20040253308A1 (en) * | 2003-04-29 | 2004-12-16 | Barr Laboratories, Inc. | Surface-treated modafinil particles |
| US20070293702A1 (en) * | 2006-02-21 | 2007-12-20 | Viviana Braude | Novel crystalline forms of armodafinil and preparation thereof |
| US20080031939A1 (en) * | 2006-03-01 | 2008-02-07 | Viviana Braude | Process for the preparation of armodafinil |
| US20090048464A1 (en) * | 2007-08-16 | 2009-02-19 | Boaz Gome | Purification of armodafinil |
| US7960586B2 (en) | 2007-08-16 | 2011-06-14 | Teva Pharmaceutical Industries Ltd. | Purification of armodafinil |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1260501A1 (en) | 2002-11-27 |
| CA2378418C (en) | 2007-11-27 |
| US20020183552A1 (en) | 2002-12-05 |
| IL143106A (en) | 2005-11-20 |
| CA2378418A1 (en) | 2002-11-13 |
| IL143106A0 (en) | 2002-04-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6649796B2 (en) | Process for the preparation of acetamide derivatives | |
| JP4872668B2 (ja) | ２−アミノ−５−ヨード安息香酸の製造方法 | |
| KR100434991B1 (ko) | N-메틸-n'-니트로구아니딘의 제조 방법 | |
| JP2005526049A (ja) | ベンゾイソキサゾールメタンスルホニルクロリドの調製及びゾニスアミドを形成するためのそのアミド化の方法 | |
| JP4700880B2 (ja) | Ｎ−メチル−ｎ’−ニトログアニジンの製造方法 | |
| EP1440970B1 (en) | Benzenesulfonic acid salt of 1-(6-halogeno-2-benzothiazolyl)ethylamine | |
| US6790977B2 (en) | Process for preparing 3,4-dihydroxy-benzonitrile | |
| JP2006131568A (ja) | ヒドロキシナフトエ酸ヒドラジドおよびその誘導体ならびにその製造方法 | |
| JP3020011B2 (ja) | ヘキサヒドロピリダジン−１，２−ジカルボキシ誘導体の製造法 | |
| JPH0859640A (ja) | シアノイミノ−１，３−チアゾリジン類の製造方法 | |
| JP4522263B2 (ja) | ベンジルアミン誘導体の製造方法 | |
| JPH0645609B2 (ja) | Ｎ−スルフアミル−３−（２−グアニジノ−チアゾ−ル−４−イル−メチルチオ）−プロピオンアミジンの製造方法 | |
| KR100264067B1 (ko) | 3-히드록시메틸-1-프로파르길이미다졸리딘-2,4-디온의 제조방법 | |
| US6680388B2 (en) | Method for preparing substituted 5-amino-N-phenyl-1,2,4-triazole-3-sulfonamides | |
| CN111039838B (zh) | 一种3-乙酰巯基-2-甲基丙酸的制备方法 | |
| CA1130305A (en) | Process for the preparation of n,n'-disubstituted 2-naphthaleneethanimidamide and intermediates used therein | |
| EP0853077B1 (en) | Process for producing alkyl 3-amino-4-substituted benzoates | |
| JP3257779B2 (ja) | タートラニル酸類の製造法 | |
| EP1321455B1 (en) | A process for the preparation of 1-(3-trifluoromethylphenyl)-2-(2-benzoyloxyethylamino)-propane | |
| JP3647915B2 (ja) | ２−アミノ−５−ニトロフェニル酢酸及びその製造方法 | |
| KR910003635B1 (ko) | 2-(2-나프틸옥시)프로피온아닐리드 유도체의 제조방법 | |
| JPS6216445A (ja) | 不斉ヒダントインの製造における中間体 | |
| JPH06192170A (ja) | ４−ブロモメチルビフェニル化合物の製造法 | |
| EP1967511A1 (en) | Process for the preparation of a benzophenone glycine imine alkyl ester derivative | |
| JPH05320115A (ja) | Ｎ−エチル−ヒドロキシルアミン塩酸塩の製法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AS | Assignment |
Owner name: CHEMAGIS, LTD., ISRAEL Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:NADDAKA, VLADIMIR;MENASHE, NAIM;LEXNER, JAEL;AND OTHERS;REEL/FRAME:012774/0530;SIGNING DATES FROM 20020311 TO 20020324 |
|
| STCF | Information on status: patent grant |
Free format text: PATENTED CASE |
|
| AS | Assignment |
Owner name: CEPHALON, INC., PENNSYLVANIA Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:CHEMAGIS, LTD;REEL/FRAME:018385/0689 Effective date: 20060924 |
|
| FPAY | Fee payment |
Year of fee payment: 4 |
|
| FPAY | Fee payment |
Year of fee payment: 8 |
|
| FEPP | Fee payment procedure |
Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY |
|
| FPAY | Fee payment |
Year of fee payment: 12 |